OBJECTIVES: 1) In frog twitch and slow fibers, intramembranous charge movements have been observed that are believed to play a role in contractile activation. The charge in both fiber types obey the same steady-state voltage distribution and the amount agrees qualitatively with the density of 'feet' in the junctions between the transverse tubules and the sarcoplasmic reticulum. Three micro-electrode voltage clamp experiments will be performed to compare the kinetics of charge movement in both fiber types. Brief depolarizing pulses will also be applied to short slow and twitch fibers to compare the latency in the rise in tension. Results from these experiments might give clues concerning the similarities and differences of contractile activation mechanism in both fiber types. 2) The pieces of evidence relating charge movement to contractile activation have been circumstantial so far. There were hints that charge movement in slow fibers does not inactivate completely, different from the situation in twitch. Voltage clamp experiments on chronically depolarized twitch and slow fibers are planned to compare the inactivation properties of charge movement. If the preliminary results can be confirmed, the lack of inactivation of charge movement in slow fibers might be relevant to their ability to maintain tension during prolonged depolarizations. 3) D2O, dantrolene sodium, Zn ions and Mn ions are known to affect contraction in striated muscle. The effect of these pharmacological agents on the shape of strength-duration curve, the magnitude and kinetics of charge movement, and the onset of tension in both fiber types will be studied. The information so obtained might help us to understand the action of these agents on contractile activation.